Efficacy of Prolonged Anticoagulation for Primary Prevention of Venous Thromboembolic Disease in Autoimmune Hemolytic Anemia: a Prospective, Phase II, Randomized, Multicenter Study

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Brief Title

Efficacy of Prolonged Anticoagulation for Primary Prevention of Venous Thromboembolic Disease in Autoimmune Hemolytic Anemia: a Prospective, Phase II, Randomized, Multicenter Study

Official Title

Efficacy of Prolonged Anticoagulation for Primary Prevention of Venous Thromboembolic Disease in Autoimmune Hemolytic Anemia: a Prospective, Phase II, Randomized, Multicenter Study

Brief Summary

      Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease (incidence <1/100,000
      population) responsible for the destruction of red blood cells by the host immune system,
      notably through the action of autoantibodies.

      Apart from complications related to anemia, the occurrence of venous thromboembolism (VTE) in
      this population is frequent, estimated at 20-27%. The risk of VTE is highest during the
      period of hemolysis, especially during the first 3 months after the diagnosis of AIHA. This
      risk is 7.5 [4.7; 12.0] times greater than in the general population. No clinical predictive
      factor for VTE was identified and the usual factors (cancer, previous VTE, bed rest >3 days,
      surgery, age >70 years, heart or respiratory failure, myocardial infarction, stroke, obesity,
      hormone replacement therapy) were not considered. Several biological risk factors have been
      suggested (depth of anemia, bilirubin level, leukocyte count, antiphospholipid antibodies)
      but have not been confirmed in other studies.

      AIHA is therefore a risk factor for VTE in its own right, and the National Diagnostic and
      Care Protocol (NDCP) recommends the implementation of VTE prevention during acute hemolysis
      (Grade C). However, the value of this prophylaxis has never been prospectively evaluated and
      its duration is empirical. In practice, low-molecular-weight heparin (LMWH) is generally used
      during "flare-ups" of AIHA (diagnosis and relapse) in hospitalized patients, but is rarely
      continued beyond the hospital phase when VTE also occurs in ambulatory patients.

      Thus, we hypothesize that prolonged preventive anticoagulation during the 12-week risk period
      following diagnosis or relapse of AIHA could decrease the incidence of VTE.

      In orthopedic surgery, this strategy has been proven to decrease VTE from 50% to 10-15%. In
      certain high-risk medical situations, prolonged prophylaxis with apixaban has been shown to
      decrease the occurrence of VTE from 10.2% to 4.2% in solid cancers4 and from 4-11% to 2% in
      myeloma.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Occurrence of clinical venous thromboembolic events (deep vein thrombosis (DVT) and pulmonary embolism (PE))


Condition

Prolonged Anticoagulation

Intervention

treatment "intervention"

Study Arms / Comparison Groups

 "intervention" group
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

72

Start Date

November 2021

Completion Date

May 2025

Primary Completion Date

May 2025

Eligibility Criteria

        Inclusion Criteria:

          -  Patient aged ≥ 18 years

          -  Patient with a diagnosis of primary or secondary autoimmune hemolytic anemia (AIHA)
             (infections, hematologic diseases, systemic diseases), according to the following
             criteria:

          -  Hemoglobin <12 g/dL

          -  and decreased haptoglobin (<0.4 g/L)

          -  and positive direct antiglobulin test (direct Coombs test) (IgG +/- C3d)

          -  Patient is treatment-naive for disease or relapse

          -  Patient with an estimated life expectancy of more than 6 months

          -  Patient who provided free, written and informed consent

        Exclusion Criteria:

          -  Patients with immediate symptomatic VTE, confirmed by appropriate complementary
             examinations (venous Doppler of the lower limbs, thoracic angioscanner or pulmonary
             scintigraphy).

          -  Patients on curative anticoagulation (venous thromboembolic disease, atrial
             fibrillation)

          -  Patient on dual antiaggregation treatment

          -  Patient with active bleeding

          -  Patient with a known condition or lesion at risk of bleeding

          -  Patient with ischemic stroke with hemorrhagic transformation within 6 months prior to
             inclusion

          -  Patient with a contraindication to apixaban:

          -  Known hypersensitivity to the molecule or to any of the excipients,,

          -  thrombocytopenia <100 G/L,

          -  kidney failure (glomerular filtration rate < 30 ml/min/1.73m²)

          -  Active liver disease (liver failure defined as Factor V <50% or INR >1.5, ALT
             elevation >2 times the upper limit of normal or conjugated/direct bilirubin elevation
             >1.5 times the upper limit of normal)

          -  Patients receiving concomitant CYP3A4 inducers (rifampin, phenytoin, carbamazepine,
             phenobarbital, St. John's Wort) or CYP3A4 inhibitors (azole antifungals, HIV protease
             inhibitors), if these therapies cannot be discontinued or modified

          -  Patients with a contraindication to enoxaparin:

          -  allergy to the drug

          -  history of heparin-induced thrombocytopenia

          -  Patient with cold agglutinin-related AHAI (C3d-positive ADT alone with identification
             of cold agglutinins)

          -  Patient with severe disorders of hemostasis:

          -  hypofibrinogenemia < 2 g/L,

          -  disseminated intravascular coagulation (APTT prolongation>1.2, and PT<50%, and
             thrombocytopenia<100 G/L, and D-Dimer >500 µg/L)

          -  hemophilia

          -  Patient whose clinical condition requires hospitalization in an intensive care unit

          -  Patient who has already participated in the study

          -  Patient not affiliated to national health insurance

          -  Patient under legal protection (curatorship, guardianship)

          -  Patient subject to a measure of legal protection

          -  Pregnant, parturient or breastfeeding women

          -  Patient with physiological capacity to procreate (having had her first menstrual
             period and not menopausal and not presenting permanent sterility (hysterectomy,
             bilateral salpingectomy, bilateral oophorectomy)) and unable to have effective
             contraception (i.e., provided by an estrogen-progestin oral contraceptive or
             progestogen, a contraceptive implant, an intrauterine device or a tubal ligation)

          -  Patient of legal age who is unable to provide consent
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 03.80.29.34.32, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT05089227

Organization ID

AUDIA PHRCI 2019


Responsible Party

Sponsor

Study Sponsor

Centre Hospitalier Universitaire Dijon


Study Sponsor

, , 


Verification Date

October 2021